The effect of pilocarpine on dental caries in patients with primary Sjögren's syndrome: a database prospective cohort study.

BACKGROUND: Primary Sjögren's syndrome (pSS) is associated with dental caries. Pilocarpine, a salivary stimulant, can improve the amount and flow rate of saliva in patients with pSS. This study aimed to assess whether the risk of dental caries decreases with the use of pilocarpine in patients with pSS. METHODS: For this prospective cohort study, we identified pSS patients from the catastrophic illnesses registry of the National Health Insurance Research Database of Taiwan between 2009 and 2013. We divided participants into pilocarpine and non-user groups based on the pilocarpine prescriptions available during the first 3-month follow-up. The primary endpoint was dental caries. The secondary endpoints were periodontitis and oral candidiasis. We compared the risk of these oral manifestations using the Cox proportional hazard model. RESULTS: A total of 4973 patients with new-onset pSS were eligible for analysis. After propensity score matching, we included 1014 patients in the pilocarpine group and 2028 patients in the non-user group. During the mean follow-up of 2.6 years, the number of events was 487 in the pilocarpine group (48.0%) and 1047 in the non-user group (51.6%); however, the difference was not significant (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.82 to 1.06). Furthermore, there was no significant difference between groups regarding risk of periodontitis (HR 0.91, 95% CI 0.81 to 1.03) and oral candidiasis (HR 1.16, 95% CI 0.70 to 1.94). CONCLUSION: Pilocarpine may have no protective effect on dental caries, periodontitis, or oral candidiasis in patients with pSS.

Novel bifurcation stents coated with bioabsorbable nanofibers with extended and controlled release of rosuvastatin and paclitaxel.

A novel bifurcation stent coated with bioabsorbable nanofibers that deliver the extended and controlled release of rosuvastatin and paclitaxel was developed. Bioabsorbable bifurcation stents, consisting of a double-slit tubular main body and two spiral branches, were manufactured. Bi-layered poly (lactic-co-glycolic acid) nanofibers that contained rosuvastatin and paclitaxel were used for treating the stents. Various properties of the fabricated stents, including compression strengths, collapse pressure, water contact angle and flow properties within a circulation model, were quantified. In vitro nanofibrous elution chromatography assays from the drug-loading bifurcation stents were carried out for the release patterns of pharmaceuticals. The effectiveness of eluted rosuvastatin and paclitaxel in inhibiting the adhesion of platelets as well as the proliferation of smooth muscle cells (SMCs) were studied, respectively. The experimental results suggest that bioabsorbable nanofibrous bifurcation stents released high concentrations of rosuvastatin and paclitaxel for 27 and 70 days, respectively. The eluted drugs of rosuvastatin and paclitaxel effectively reduced adherent platelets and the proliferation of SMCs. The developed bioabsorbable nanofibrous bifurcation stents herein may provide a promising means of treating cardiovascular bifurcation lesions.

Biodegradable Cable-Tie Rapamycin-eluting Stents.

"Cable-tie" type biodegradable stents with drug-eluting nanofiber were developed to treat rabbit denuded arteries in this study. Biodegradable stents were fabricated using poly-L-lactide film following being cut and rolled into a cable-tie type stent. Additionally, drug-eluting biodegradable nanofiber tubes were electrospun from a solution containing poly (lactic-co-glycolic acid), rapamycin, and hexafluoroisopropanol, and then mounted onto the stents. The fabricated rapamycin-eluting cable-tie stents exhibited excellent mechanical properties on evaluation of compression test and collapse pressure, and less than 8% weight loss following being immersed in phosphate-buffered saline for 16 weeks. Furthermore, the biodegradable stents delivered high rapamycin concentrations for over 4 weeks and achieved substantial reductions in intimal hyperplasia associated with elevated heme oxygenase-1 and calponin level on the denuded rabbit arteries during 6 months of follow-up. The drug-eluting cable-tie type stents developed in this study might have high potential impacts for the local drug delivery to treat various vascular diseases.

Augmentation of diabetic wound healing and enhancement of collagen content using nanofibrous glucophage-loaded collagen/PLGA scaffold membranes.

This work developed nanofibrous drug-loaded collagen/poly-D-L-lactide-glycolide (PLGA) scaffold membranes that provided the sustained release of glucophage for the wounds associated with diabetes. PLGA, glucophage, and collagen were firstly dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol and were spun into nanofibrous membranes by electrospinning. High-performance liquid chromatography assay was used to characterize the in vivo and in vitro release rates of the pharmaceuticals from the membranes. High concentrations of glucophage were released for over three weeks from the nanofibrous membranes. The nanofibrous glucophage-loaded collagen/PLGA membranes were more hydrophilic than collagen/PLGA membranes and exhibited a greater water-containing capacity. The glucophage-loaded collagen/PLGA membranes markedly promoted the healing of diabetic wounds. Moreover, the collagen content of diabetic rats using drug-eluting membranes was higher than that of the control rats, because of the down-regulation of matrix metalloproteinase 9. The experimental results herein suggest that the nanofibrous glucophage-loaded collagen/PLGA membranes had effect for increasing collagen content in treating diabetic wounds and very effective promoters of the healing of such wounds in the early stages.

Promoting Diabetic Wound Therapy Using Biodegradable rhPDGF-Loaded Nanofibrous Membranes: CONSORT-Compliant Article.

The nanofibrous biodegradable drug-loaded membranes that sustainably released recombinant human platelet-derived growth factor (rhPDGF-BB) to repair diabetic wounds were developed in this work.rhPDGF-BB and poly(lactic-co-glycolic acid) (PLGA) were mixed in hexafluoroisopropyl alcohol, followed by the electrospinning of the solutions into biodegradable membranes to equip the nanofibrous membranes. An elution technique and an enzyme-linked immunosorbent assay kit were used to determine the rhPDGF-BB release rates in vitro and in vivo from this membrane. Eighteen Sprague-Dawley streptozotocin-induced diabetic rats were randomized into 3 groups: rhPDGF-BB-loaded nanofibrous membrane group, PLGA only membrane group, and conventional gauze sponge group for the wound associated with diabetes of rat in each group.The nanofibrous biodegradable membranes released effective concentrations of rhPDGF-BB for over 21 days. The nanofibrous rhPDGF-BB-loaded PLGA membranes contained more water and were further hydrophilic than PLGA only fibers. The rhPDGF-BB-loaded PLGA membranes considerably helped the diabetic wounds repairing. Furthermore, the proliferative cells and angiogenesis of rats associated with diabetes by rhPDGF-BB-loaded nanofibrous membranes were greater than those of other groups, owing to the increased matrix metalloproteinase 9.These biodegradable rhPDGF-BB-loaded membranes were effective in treating diabetic wounds as very advanced accelerators during the initial phases of wound-healing process.

Acceleration of re-endothelialization and inhibition of neointimal formation using hybrid biodegradable nanofibrous rosuvastatin-loaded stents.

Incomplete endothelialization and neointimal hyperplasia of injured arteries can cause acute and late stent thromboses. This work develops hybrid stent/biodegradable nanofibers for the local and sustained delivery of rosuvastatin to denuded artery walls. Biodegradable nanofibers were firstly prepared by dissolving poly(D,L)-lactide-co-glycolide and rosuvastatin in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution was then electrospun into nanofibrous tubes, which were mounted onto commercially available bare-metal stents. The in vitro release rates of the pharmaceuticals from the nanofibers were determined using an elution method and a high-performance liquid chromatography assay. The experimental results thus obtained suggest that the biodegradable nanofibers released high concentrations of rosuvastatin for four weeks. The effectiveness of the local delivery of rosuvastatin in reducing platelets was studied. The tissue inflammatory reaction caused by the hybrid stents that were used to treat diseased arteries was also documented. The proposed hybrid stent/biodegradable rosuvastatin-loaded nanofibers contributed substantially to the local and sustainable delivery of a high concentration of drugs to promote re-endothelialization, improve endothelial function, reduce inflammatory reaction, and inhibit neointimal formation of the injured artery. The results of this work provide insight into how patients with a high risk of stent restenosis should be treated for accelerating re-endothelialization and inhibiting neointimal hyperplasia.

Promoting endothelial recovery and reducing neointimal hyperplasia using sequential-like release of acetylsalicylic acid and paclitaxel-loaded biodegradable stents.

INTRODUCTION: This work reports on the development of a biodegradable dual-drug-eluting stent with sequential-like and sustainable drug-release of anti-platelet acetylsalicylic acid and anti-smooth muscle cell (SMC) proliferative paclitaxel. METHODS: To fabricate the biodegradable stents, poly-L-lactide strips are first cut from a solvent-casted film. They are rolled onto the surface of a metal pin to form spiral stents. The stents are then consecutively covered by acetylsalicylic acid and paclitaxel-loaded polylactide-polyglycolide nanofibers via electrospinning. RESULTS: Biodegradable stents exhibit mechanical properties that are superior to those of metallic stents. Biodegradable stents sequentially release high concentrations of acetylsalicylic acid and paclitaxel for more than 30 and 60 days, respectively. In vitro, the eluted drugs promote endothelial cell numbers on days 3 and 7, and reduce the proliferation of SMCs in weeks 2, 4, and 8. The stents markedly inhibit the adhesion of platelets on days 3, 7, and 14 relative to a non-drug-eluting stent. In vivo, the implanted stent is intact, and no stent thrombosis is observed in the stent-implanted vessels without the administration of daily oral acetylsalicylic acid. Promotion of endothelial recovery and inhibition of neointimal hyperplasia are also observed on the stented vessels. CONCLUSION: The work demonstrates the efficiency and safety of the biodegradable dual-drug-eluting stents with sequential and sustainable drug release to diseased arteries.